The overall goals of the proposed research are to study the biochemistry of heparan sulfate, determining the pathway of its metabolism and intracellular flow, the manner in which its structure and amounts are regulated, and its role in the regulation of cell division. Most of the work will be done with an hepatocyte cell line that has been used in previous work, but a number of other cell types will be surveyed to determine whether the unusual features of HS metabolism and activity observed in hepatocytes are general properties of all cells that produce heparin sulfate. Detailed analysis of heparan sulfate proteoglycan from log and confluent cells will be carried out to determine the structural features that are correlated with the difference in the effects of these two species of heparan sulfate proteoglycan on cell division. Alterations in the growth behavior of hepatocytes with mutations the alter heparan sulfate proteoglycan metabolism will be studied, and attempts will be made to correlate the metabolic changes that result from mutations with growth behavior. Finally, the specific cell surface receptor that mediates the heparan sulfate proteoglycan binding and endocytosis will be isolated and its structure and biological activities will be determined.